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DE637385C - Process for the preparation of 2, 4-dioxo-1, 3, 3-trialkyl- and -1, 3, 3, 6-tetraalkyltetrahydropyridines - Google Patents

Process for the preparation of 2, 4-dioxo-1, 3, 3-trialkyl- and -1, 3, 3, 6-tetraalkyltetrahydropyridines

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Publication number
DE637385C
DE637385C DEH144863D DEH0144863D DE637385C DE 637385 C DE637385 C DE 637385C DE H144863 D DEH144863 D DE H144863D DE H0144863 D DEH0144863 D DE H0144863D DE 637385 C DE637385 C DE 637385C
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DE
Germany
Prior art keywords
dioxo
parts
weight
preparation
tetraalkyltetrahydropyridines
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Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
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DEH144863D
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German (de)
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HOFFMANNI LA ROCHE and CO AKT GE
Original Assignee
HOFFMANNI LA ROCHE and CO AKT GE
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Application filed by HOFFMANNI LA ROCHE and CO AKT GE filed Critical HOFFMANNI LA ROCHE and CO AKT GE
Priority to DEH144863D priority Critical patent/DE637385C/en
Application granted granted Critical
Publication of DE637385C publication Critical patent/DE637385C/en
Expired legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/69—Two or more oxygen atoms

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pyridine Compounds (AREA)

Description

Verfahren zur Herstellung von 2, 4-Dioxo-1, 3,3 -trialkyl-und -1, 3, 3, 6-tetraalk#,ltetrahyd'ropyridinen Es wurde nun gefunden, daß die nach dem Verfahren des Patents 634 284 erhältlichen 2, q.-Dioxo-3, 3-dialkyltetrahydropyridine sowie die 2, 4-Dioxo-3, 3-di:alkyl-6-methyltetrahydropyridine, die nach dem Verfahren,des Patents 634 285 gewonnen werden, eine neue Klasse von therapeutisch wertvollen Verbindungen liefern, wenn man sie am Stickstoff alkvliert. Zur erfolgreichen Alkylierung ist es erforderlich, das Alkylierungsmittel auf die Alkalisalze der 2, 4-Dioxo-3, 3-dialkyltetralivdropyridine bzw. ihrer in 6-Stellung nietlivlierten Abkömmlinge einwirken zu lassen. Trotzdem die Ausgangsverbindungen in starken Säuren löslich sind, führt die Einwirkung von z. B. Halogenalkvl bei Abwesenheit von Alkali nicht zum Ziel. So gelang es auch nicht, durch Erhitzen mit Halogenalkvl das 2, 4-Dioxvpyridin zu alkylieren (Ber. d. D. Chem. Ges. 31, [1898] S. 169o).Process for the preparation of 2,4-dioxo-1, 3,3- trialkyl- and -1, 3, 3, 6-tetraalk #, l-tetrahydropyridines It has now been found that the 2 , q.-Dioxo-3, 3-dialkyltetrahydropyridines and the 2, 4-dioxo-3, 3-di: alkyl-6-methyltetrahydropyridines, which are obtained according to the method of patent 634 285, a new class of therapeutically valuable compounds deliver when they are alkalized to nitrogen. For successful alkylation it is necessary to allow the alkylating agent to act on the alkali metal salts of the 2,4-dioxo-3, 3-dialkyltetralivdropyridines or their derivatives riveted in the 6-position. Despite the fact that the starting compounds are soluble in strong acids, the action of z. B. Halogenalkvl in the absence of alkali is not the goal. It was also not possible to alkylate the 2,4-dioxvpyridine by heating with haloalkylene (Ber. D. D. Chem. Ges. 31, [1898] p. 169o).

Die Schmelzpunkte der neuen Verbindungen liegen niedrig, so daß sie zum Teil bei gewöhnlicher Temperatur flüssig sind. Sie lösen sich sehr leicht in organischen Lösungsmitteln; auch sind sie in Wasser meistens leichter löslich als die entsprechenden Ausgangsverbindungen. Die niedrigeren Glieder können im luftverdünnten Raum unzersetzt" destilliert werden. In Alkalien sind sie unlöslich. Im Tierversuch erzeugen sie einen tiefen, ziemlich flüchtigen Schlaf. Beispiel i Zu einer Lösung von 167 Gewichtsteilen 2, 4-Dioxo-3, 3-diäthyltetrahydropyridin in 9oo Gewichtsteilen Wasser und 129 Gewichtsteilen Natronlauge WO/,) läßt man unter gutem Rühren 126 Gewichtsteile Dimethylsulfat langsam einfließen. Die Umsetzung geht sofort unter Erwärmen vor sich. Kurz nach Beendigung der Zugabe tritt neutrale Reaktion ein. Zur Reinigung kann das ausgeschiedene i-Methv 1-2, 4-dioxo-3, 3-diäthyltetrahydropyridin in Äther oder Benzol aufgenommen und im luftverdünnten Raume destilliert «-erden (Kp. bei etwa i4 mm: 152 bis 15.4°). Aus Petroläther kristallisiert es in farblosen glänzenden Tafeln vom Schmelzpunkt 74 bis 75o.The melting points of the new compounds are low, so they are partly liquid at ordinary temperature. They dissolve in very easily organic solvents; they are also mostly more easily soluble in water than the corresponding starting compounds. The lower limbs can be aerated Room undecomposed ". They are insoluble in alkalis. In animal experiments they produce a deep, rather fleeting sleep. Example i To a solution of 167 parts by weight of 2,4-dioxo-3, 3-diethyltetrahydropyridine in 900 parts by weight Water and 129 parts by weight of sodium hydroxide solution WO /,) are allowed to 126 with thorough stirring Slowly pour in parts by weight of dimethyl sulfate. The implementation goes under immediately Warming up in front of you. A neutral reaction occurs shortly after the addition is complete. The precipitated i-methoxy 1-2, 4-dioxo-3, 3-diethyltetrahydropyridine can be used for purification taken up in ether or benzene and distilled in an air-thinned room (Kp. At about i4 mm: 152 to 15.4 °). From petroleum ether it crystallizes into colorless ones shiny tablets with a melting point of 74 to 75o.

Beispiel 2 205 Gewichtsteile 2, 4-Dioxo-3, 3-dia.llyl-6-methyltetrahydropyridin werden in iooo Raumteilen n-Natronlauge gelöst. Man fügt der lebhaft geriihrten Lögung i-,i Gewichtsteile Allylbromid und o,.4 Gewichtsteile Kupferpulver zu, wonach unter merklicher Erwärmung die Umsetzung vor sich geht. Nach i Stunde fortgesetzten Rührens nimmt man das nölig abgeschiedene 1, 3, 3-Triallyl-6-methyl-2, 4-dioxotetrahydropyridin in Benzol auf und destilliert im luftverdünnten Raum. Die neue Verbindung wind als nahezu farbloses Öl gewonnen, das bei etwa 14 mm Druck zwischen 183 und z86° siedet.Example 2 205 parts by weight of 2,4-dioxo-3, 3-dia.llyl-6-methyltetrahydropyridine n-sodium hydroxide solution is dissolved in 1,000 parts by volume. One adds the vigorously stirred Solution i-, i parts by weight of allyl bromide and 0.4 parts by weight of copper powder, after which the implementation goes on with noticeable warming. After one hour continued The 1,3,3-triallyl-6-methyl-2,4-dioxotetrahydropyridine which has precipitated in oil is taken while stirring in benzene and distilled in the air diluted Space. The new connection wind obtained as an almost colorless oil, which at about 14 mm pressure between 183 and z86 ° boils.

Beispiel 3 ' Man löst 6o :Gewichtsteile Kaliumhydrox@2; in 8öo Gewichtsteilen absolutem Alkohol, gibt r67 Gewichtsteile 2, 4-Dioxo-3, 3-diäthyltetrahydropyridin und iio Gewichtsteile Äthylbromid zu und erwärmt im Autoklaven unter Rühren i2 Stunden, auf ioo°. Zur Gewinnung des Umsetzungsproduktes filtriert man vom ausgeschiedenen Kaliumbromid ab und destilliert den Alkohol ab, entfernt erneut ausgeschiedenes Salz und destilliert nunmehr unter vermindertem Druck. Das 2, 4-Dioxo-1, 3, 3-Triäthyltetrahydropyridin geht unter 14 mm Druck zwischen 148 und 150' als farbloses, nicht erstarrendes Öl über.Example 3 Dissolve 6o: parts by weight of potassium hydroxide @ 2; in 80 parts by weight absolute alcohol, gives 67 parts by weight of 2,4-dioxo-3, 3-diethyltetrahydropyridine and iio parts by weight of ethyl bromide and heated in the autoclave with stirring for i2 hours, to ioo °. To recover the reaction product, the precipitated product is filtered off Potassium bromide and distills off the alcohol, removes again excreted Salt and now distilled under reduced pressure. The 2,4-dioxo-1, 3, 3-triethyltetrahydropyridine goes under 14 mm pressure between 148 and 150 'as a colorless, non-solidifying oil above.

Beispiel 4 Man löst 19.5 Gewichtsteile 2, 4-Dioxo-3, 3-di-n-propyltetrahydropyridin in 92o Gewichtsteilen einer Natronlauge, die 4o Gewichtsteile Na0 H enthält. Bei gewöhnlicher Temperatur läßt man unter gutem Rühren während etwa 1/2 Stunde 126 Gewichtsteile Dimnethylsulfat einlaufen. Sobald nach Beendigung der Zugabe von Dimethyl- @`ülfat neutrale Reaktion eingetreten ist, kann ui- G.e@nung des Umsetzungsproduktes die äzsersg ~.tösung nach Durchschütteln mit .`@ einem' mit Wasser nicht mischbaren organischen-Lösungsmittel, beispielsweise Äther, abgetrennt werden. Nach Verjagen des Lösungsmittels wird das 2, 4-Dioxo-i-methyl-3, 3-di-n-propyltetrahydropyridin im luftverdünnten Raume destilliert (Kp. 162 bis 164' bei etwa 14 min). Durch Umlösen aus Petroläther gewinnt man farblose Kristalle vorn Schmelzpunkt 61 bis 62°.EXAMPLE 4 19.5 parts by weight of 2,4-dioxo-3, 3-di-n-propyltetrahydropyridine are dissolved in 92o parts by weight of a sodium hydroxide solution containing 40 parts by weight of Na0H. At normal temperature, 126 parts by weight of dimethyl sulfate are run in over about 1/2 hour with thorough stirring. As soon as the addition of dimethyl @ `ülfat neutral reaction has occurred, can ui- the conversion product Äzsersg ~ .solution after shaking with .` @ a 'water-immiscible organic solvent such as ether. After the solvent has been driven off, the 2,4-dioxo-i-methyl-3,3-di-n-propyltetrahydropyridine is distilled in an air-diluted room (bp 162 to 164 'at about 14 minutes). Colorless crystals with a melting point of 61 to 62 ° are obtained by dissolving from petroleum ether.

Claims (1)

PATEINTANSPRUCH: Verfahren zur Darstellung von 2, 4-Dioxo-1, 3, 3-trialkvl- und -1, 3, 3, 6-tetraalkyltetrahydropyridinen, dadurch gekennzeichnet, daß man auf die Alkalisalze der z, 4-D.ioxo-3, 3-dialkyltetrahydropyridine oder ihrer in 6-Stellung methylierten Abkömmlinge Alkylierungsmittel einwirken läßt.PATENT CLAIM: Process for the preparation of 2, 4-Dioxo-1, 3, 3-trialkvl- and -1, 3, 3, 6-tetraalkyltetrahydropyridines, characterized in that on the alkali salts of the z, 4-D.ioxo-3, 3-dialkyltetrahydropyridines or their in the 6-position methylated derivatives allow alkylating agents to act.
DEH144863D 1935-09-05 1935-09-05 Process for the preparation of 2, 4-dioxo-1, 3, 3-trialkyl- and -1, 3, 3, 6-tetraalkyltetrahydropyridines Expired DE637385C (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
DEH144863D DE637385C (en) 1935-09-05 1935-09-05 Process for the preparation of 2, 4-dioxo-1, 3, 3-trialkyl- and -1, 3, 3, 6-tetraalkyltetrahydropyridines

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DEH144863D DE637385C (en) 1935-09-05 1935-09-05 Process for the preparation of 2, 4-dioxo-1, 3, 3-trialkyl- and -1, 3, 3, 6-tetraalkyltetrahydropyridines

Publications (1)

Publication Number Publication Date
DE637385C true DE637385C (en) 1936-10-27

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DEH144863D Expired DE637385C (en) 1935-09-05 1935-09-05 Process for the preparation of 2, 4-dioxo-1, 3, 3-trialkyl- and -1, 3, 3, 6-tetraalkyltetrahydropyridines

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2525231A (en) * 1950-10-10 J-trimethyl-z
DE946540C (en) * 1951-10-05 1956-08-02 Hoffmann La Roche Process for the preparation of alkylated dioxopiperidines

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2525231A (en) * 1950-10-10 J-trimethyl-z
DE946540C (en) * 1951-10-05 1956-08-02 Hoffmann La Roche Process for the preparation of alkylated dioxopiperidines

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